A major purpose of the proposed research is to investigate the role of the thyroid parafollicular cells in mammalian physiology. Many of the proposed studies will be carried out in the bat because its thyroid gland has been found to contain large numbers of parafollicular cells which exhibit two types of secretory granules and because parafollicular cells are parathyroid chief cells show cyclic secretory changes related to alterations in bone activity. Changes in secretory activity of bat parafollicular cells will be correlated with alterations in calcium and thyrocalcitonin metabolism. The seasonal changes in bat bone will be further investigated by examining bone tissue with both transmission and scanning electron microscopy. The effect of hibernation on bone flow and protein turnover will also be examined. Other objectives of the proposed research are as follows: (1) To determine the role of the parafollicular cell during development in the dog by determining ultrastructural changes, monoamine oxidase activity and serotonin turnover. (2) To determine the effect of drugs, such as pentagastrin, thiouracil, etc., on the storage and synthesis of serotonin by parafollicular cells. (3) To determine the function of serotonin in the thyroid and its relationship to the polypeptide calcitonin, which appears to share storage vesicles with serotonin. (4) To continue the study of intracellular secretory pathways in thyroid follicular cells. (5) Parameters of serotonin uptake by the thyroid gland will be studied. (6) Ultracentrifugation in conjunction with electron microscopy will be used for isolation and characterization of parafollicular cell storage vesicles. (7) Electron microscopic autoradiography will be used to examine the intracellular movement of proline in thyroid parafollicular cells. (8) To continue to define secretory pathways at the ultrastructural level in parafollicular cells and parathyroid chief cells. The approach is an integrated one, with biochemical and physiological methods used whenever possible with ultrastructural techniques.